Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Newly discovered cellular process helps cells respond to DNA damage

30.01.2003


Biochemical mechanism may lead to new cancer prevention and treatment strategies



Scientists at St. Jude Children’s Research Hospital have discovered a novel biochemical process that plays a critical role in helping cells in the body respond to DNA damage, such as that caused by exposure to radiation, environmental toxins or free radicals.
The findings could lead to new approaches to prevent cancer, better ways to treat cancer and to the development of sensitive methods determining whether people have been exposed to radiation or environmental toxins, according to the researchers.

A report on this discovery, published in the current issue of the journal Nature, describes this critical early step in a cell’s response to DNA damage. This step, a chemical modification of an enzyme called ATM, allows the enzyme to initiate a series of events that ultimately halt the growth of a damaged cell and help the cell survive.



The finding is important because DNA damage caused by radiation and environmental toxins can lead to mutations or cell death, and can also contribute to the development of cancers.

Michael Kastan, M.D., Ph.D., chair of the Department of Hematology-Oncology at St. Jude and Christopher Bakkenist, Ph.D., also of St. Jude co-authored the research.

The St. Jude researchers found that ATM is activated by a signal from damaged DNA only seconds after the damage occurs. The activated ATM, in turn, activates other proteins by attaching a molecule called "phosphate" to them in a process called phosphorylation. This sets off a cascade of biochemical reactions that amplifies the initial ATM response.

Among the proteins phosphorylated by ATM are Brca1 and p53. It was already known that these proteins play important roles in preventing cancer, and that mutated forms of Brca1 and p53 are responsible for inherited cancers, such as familial breast cancer. The new St. Jude findings thus provide new insights into the way cells signal to both Brca1 and p53 following DNA damage.

The scientists are hopeful that they can use this information to improve therapy for many types of tumors.

"Because ATM is central to a cell’s response to irradiation, blocking its activation or activity might make virtually any type of tumor much more sensitive to radiation therapy," Kastan said. "The new molecular mechanisms identified here should allow us to achieve this aim by blocking ATM activity, which would make tumors more sensitive to radiation."

The St. Jude researchers also developed an antibody that specifically recognizes activated ATM, and thus identifies only those ATM molecules that are responding to DNA damage. "Our technique for identifying activated ATM is so sensitive that we’ve been able to show that it takes only a couple of breaks in the entire DNA of the cell to activate and initiate all of the cell’s response mechanisms," Kastan said.

The identification of these molecular mechanisms and the development of specific antibodies against activated ATM might also provide a very sensitive way to determine if cells in a person have been exposed to an agent or toxin that damages DNA, according to Kastan.

"Such an assay has many obvious potential uses," Kastan said, "including the assessment of exposure to dangerous agents in the environment." Another potential clinical benefit of these discoveries applies to cancer prevention. Since damage to the DNA appears to contribute to the vast majority of human cancers, enhancing the response of cells to DNA damage could reduce cancer development, Kastan noted. Therefore, the discovery of how ATM is activated could help guide the development of ways to improve cellular responses to DNA damage, including responses to oxidative stress that are either induced or natural.

"Based on the insights we’ve gained from our findings, we may be able to develop ways to activate ATM and thereby prevent or reduce the problems associated with DNA damage," Kastan said.



This work was supported by grants from the National Cancer Institute and National Institute of Environmental Health Sciences.

About St. Jude Children’s Research Hospital
St. Jude Children’s Research Hospital, in Memphis, Tennessee, was founded by the late entertainer Danny Thomas. The hospital is an internationally recognized biomedical research center dedicated to finding cures for childhood catastrophic diseases. The hospital’s work is supported through funds raised by the American Lebanese Syrian Associated Charities (ALSAC).

ALSAC covers all costs not covered by insurance for medical treatment rendered at St. Jude Children’s Research Hospital. Families without insurance are never asked to pay.

Bonnie Cameron | EurekAlert!
Further information:
http://www.stjude.org/

More articles from Life Sciences:

nachricht Discovery of a Key Regulatory Gene in Cardiac Valve Formation
24.05.2017 | Universität Basel

nachricht Carcinogenic soot particles from GDI engines
24.05.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

Im Focus: Using graphene to create quantum bits

In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.

In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

Physicists discover mechanism behind granular capillary effect

24.05.2017 | Physics and Astronomy

Measured for the first time: Direction of light waves changed by quantum effect

24.05.2017 | Physics and Astronomy

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>